NFAT4 movement in native smooth muscle. A role for differential Ca(2+) signaling
Stevenson, Andra S. ; Gomez, Maria LU
; Hill-Eubanks, David C.
and Nelson, Mark T.
(2001)
In Journal of Biological Chemistry
276(18).
p.15018-15024
- Abstract
- The transcription factor NFAT (nuclear factor of activated T-cells) plays a central role in mediating Ca(2+)-dependent gene transcription in a variety of cell types. Sustained increases in intracellular calcium concentration ([Ca(2+)]i) are presumed to be required for NFAT dephosphorylation by the Ca(2+)/calmodulin-dependent protein calcineurin and its subsequent nuclear translocation. Here, we provide the first identification and characterization of NFAT in native smooth muscle, showing that NFAT4 is the predominant isoform detected by reverse transcriptase-polymerase chain reaction and Western blot analysis. PDGF induces NFAT4 translocation in smooth muscle, leading to an increase in NFAT transcriptional activity. NFAT4 activation by... (More)
- The transcription factor NFAT (nuclear factor of activated T-cells) plays a central role in mediating Ca(2+)-dependent gene transcription in a variety of cell types. Sustained increases in intracellular calcium concentration ([Ca(2+)]i) are presumed to be required for NFAT dephosphorylation by the Ca(2+)/calmodulin-dependent protein calcineurin and its subsequent nuclear translocation. Here, we provide the first identification and characterization of NFAT in native smooth muscle, showing that NFAT4 is the predominant isoform detected by reverse transcriptase-polymerase chain reaction and Western blot analysis. PDGF induces NFAT4 translocation in smooth muscle, leading to an increase in NFAT transcriptional activity. NFAT4 activation by PDGF depends on Ca(2+) entry through voltage-dependent Ca(2+) channels, because its nuclear accumulation is prevented by the Ca(2+) channel blocker nisoldipine and the K(+) channel opener pinacidil. Interestingly, elevation of [Ca(2+)]i by membrane depolarization or ionomycin treatment are not effective stimuli for NFAT4 nuclear accumulation, indicating that Ca(2+) influx is necessary but not sufficient for NFAT4 activation. In contrast, membrane depolarization readily activates the Ca(2+)-dependent transcription factor CREB (cAMP-responsive element-binding protein). The calcineurin blockers CsA and FK506 also prevented the PDGF-induced NFAT4 nuclear localization. These results indicate that both the nature of the calcium signal and PDGF-induced modulation of nuclear import-export of NFAT are critical for NFAT4 activation in this tissue. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1120256
- author
- Stevenson, Andra S.
; Gomez, Maria
LU
; Hill-Eubanks, David C.
and Nelson, Mark T.
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 276
- issue
- 18
- pages
- 15018 - 15024
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:11278965
- scopus:0035805561
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M011684200
- language
- English
- LU publication?
- no
- id
- 8526ef0a-96e4-4038-b8d0-9462634d5046 (old id 1120256)
- date added to LUP
- 2016-04-01 11:52:23
- date last changed
- 2022-01-26 19:31:36
@article{8526ef0a-96e4-4038-b8d0-9462634d5046,
abstract = {{The transcription factor NFAT (nuclear factor of activated T-cells) plays a central role in mediating Ca(2+)-dependent gene transcription in a variety of cell types. Sustained increases in intracellular calcium concentration ([Ca(2+)]i) are presumed to be required for NFAT dephosphorylation by the Ca(2+)/calmodulin-dependent protein calcineurin and its subsequent nuclear translocation. Here, we provide the first identification and characterization of NFAT in native smooth muscle, showing that NFAT4 is the predominant isoform detected by reverse transcriptase-polymerase chain reaction and Western blot analysis. PDGF induces NFAT4 translocation in smooth muscle, leading to an increase in NFAT transcriptional activity. NFAT4 activation by PDGF depends on Ca(2+) entry through voltage-dependent Ca(2+) channels, because its nuclear accumulation is prevented by the Ca(2+) channel blocker nisoldipine and the K(+) channel opener pinacidil. Interestingly, elevation of [Ca(2+)]i by membrane depolarization or ionomycin treatment are not effective stimuli for NFAT4 nuclear accumulation, indicating that Ca(2+) influx is necessary but not sufficient for NFAT4 activation. In contrast, membrane depolarization readily activates the Ca(2+)-dependent transcription factor CREB (cAMP-responsive element-binding protein). The calcineurin blockers CsA and FK506 also prevented the PDGF-induced NFAT4 nuclear localization. These results indicate that both the nature of the calcium signal and PDGF-induced modulation of nuclear import-export of NFAT are critical for NFAT4 activation in this tissue.}},
author = {{Stevenson, Andra S. and Gomez, Maria and Hill-Eubanks, David C. and Nelson, Mark T.}},
issn = {{1083-351X}},
language = {{eng}},
number = {{18}},
pages = {{15018--15024}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{NFAT4 movement in native smooth muscle. A role for differential Ca(2+) signaling}},
url = {{http://dx.doi.org/10.1074/jbc.M011684200}},
doi = {{10.1074/jbc.M011684200}},
volume = {{276}},
year = {{2001}},
}